Conventional techniques for in situ synthesis and custom microarray manufacturing have been developed in the field of biological, chemical, and biochemical assaying of samples (e.g., nucleic acids, proteins, pharmaceutical compounds, and other analytes of interest), for use in sample detection, monitoring, and analysis. For example, DNA microarray technology is currently being developed for use in genomic research and diagnostic applications in which the ability to simultaneously analyze thousands of DNA sequences is beneficial. While in situ synthesis can provide enormous densities, the technique is not suitable for rapid prototyping. On the other hand, several problematic issues arise with regard to techniques relating to custom microarray printing technologies, including the size of the devices needed for sophisticated robotics, humidity and temperature control, the requirement of clean surroundings, wear and tear of the tips of pins or quills conventionally used, and expense of the equipment needed.
Microarrays are typically fabricated by printing or spotting, which entails dispensing very small volumes (i.e., the nanoliter and picoliter ranges) of sample material onto the surface of a solid substrate such as a glass slide. Both non-contact and contact dispensing techniques are being developed. Non-contact dispensing is performed by ejecting sample droplets from a dispenser onto the substrate. Currently, adaptations of ink-jet printing techniques are popular means for performing non-contact dispensing. Contact printing, on the other hand, requires direct contact of the dispensing device (e.g., capillary tubes, solid pins, split pins, and tweezers) with the substrate.
One example of a contact dispensing technique is disclosed in U.S. Pat. No. 6,110,426 to Shalon et al., which describes a method for fabricating microarrays of biological samples by using a capillary reagent dispenser that must contact the microarray surface to dispense its contents. In another example, arrays of pins are dipped into a sample solution and the tips of the pins are then brought into contact with a slide surface, leaving sample spots on the surface. The diameter of each pin primarily determines the size of the sample dispensed onto the surface. In another technique, a ring is dipped into the sample solution to draw sample liquid across its opening. A solid pin is then thrust through the opening and tapped against the substrate to dispense a portion of the sample onto the substrate. When employed to fabricate more than a few microarrays, the use of such contact techniques are undesirably slow processes. Moreover, these techniques have created problems with uniformity in sample volume, equipment durability, and spot reproducibility.
Non-contact dispensing techniques based on ink-jet technology typically entail the use of a piezoelectric crystal or a syringe-solenoid actuating device. For example, a piezoelectric crystal can be placed in contact with a capillary tube containing a sample fluid. By applying a voltage to the crystal is biased to deform at a rapid rate over a small deformation distance. As a result, the capillary is vibrated and ejects droplets from its tip. The high frequency response of the crystal and the small distance through which it vibrates enables thousands of droplets of small volume to be dispensed. On the other hand, the syringe-solenoid device is constructed by connecting a syringe pump between a reservoir and a solenoid valve through tubing. Actuation of the syringe creates liquid pressure in the system, enabling the valve to dispense samples from its outlet. This latter system requires a liquid media such as water. While such non-contact array printing methods address some of the afore-mentioned problems relating to microarray printing, they do not solve all of them and add new problems of their own. Keeping the inkjet orifices free of contaminants is one such problem. Moreover, air bubbles can develop that impair reliability. In addition, the size or footprint of the system can still be a problem.
In another example, U.S. Pat. No. 6,231,177 to Cherukuri et al. discloses a device that uses electrohydrodynamic (EHD) micropumps to dispense fluid from orifices onto textured paper. While the device can be scaled to a small size, it is similar to inkjet devices and burdened by similar problems.
It is therefore acknowledged by persons skilled in the art that ongoing development is needed to provide improved methods for non-contact microarray printing.